E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | llt |
E.1.2 | Classification code | 10010952 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of 500 mcg roflumilast once daily on exacerbation rate, pulmonary function, COPD symptoms, dyspnea, health related quality of life and health care resource use |
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of roflumilast |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
· Written informed consent · Age =40 years · History of COPD for at least 12 months as defined in the ATS/ERS consensus statement (Standards for the Diagnosis and Management of patients with COPD, 2004) and chronic productive cough for 3 months in each of the 2 years prior to baseline visit V0 (if other causes of productive cough have been excluded) · FEV1/FVC ratio (post-bronchodilator) = 70% · FEV1 (post-bronchodilator) = 50% of predicted · At least one documented COPD exacerbation (as defined by the need for oral or parenteral glucocorticosteroid intake and/or hospitalization) within one year prior to study baseline visit V0 · Not suffering from any concomitant disease that might interfere with study procedures or evaluation · Current smoker or former smoker (smoking cessation at least one year ago) with a smoking history of at least 20 pack years · Availability of a chest x-ray or CT-scan dated a maximum of 6 months prior to study baseline visit V0 or willingness to have a chest x-ray or CT-scan performed at visit V0
|
|
E.4 | Principal exclusion criteria |
· COPD exacerbation indicated by a treatment with oral or parenteral glucocorticosteroids and/or hospitalization not resolved at V0 · Diagnosis of asthma and/or other relevant lung disease (e.g. history of bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], and active tuberculosis) · Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator) · Pregnancy, breast feeding, oocyte donation or oocyte implantation planned during the trial · Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, unless they are surgically sterilized/hysterectomized or post-menopausal > 1 year or who are not using any other method of contraception considered sufficiently reliable by the investigator in individual cases · Chronic gastrointestinal disorders associated with a history of recurrent gastrointestinal bleedings within the last 12 months preceding the baseline visit V0 · Participation in another clinical study (use of investigational product) within 30 days preceding the baseline visit V0 · Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline visit V0 · Use of disallowed drugs · Use of immunosuppressive medications within 4 weeks prior to baseline (e.g. cyclosporine, methotrexate, TNF alpha receptors or antibodies, gold, azothiaprine) · Known alpha-1-antitrypsin deficiency · Known infection with HIV and/or active hepatitis · Diagnosis, treatment, or remission of any cancer (other than basal cell carcinoma) within 5 years prior to study start, · Clinically significant cardiopulmonary abnormalities (diagnosed clinically or by x-ray/CT-scans/ ECG) that are not related to COPD and that require further evaluation · Clinically relevant ECG findings (e.g. acute or recent myocardial infarction, clinically significant arrhythmia) · Alcohol or drug abuse · Suspected hypersensitivity and/or contraindication to any ingredients of the study medication (roflumilast) or rescue medication · Patients not able to follow study procedures e.g. language problems, psychological disorders · Suspected non-compliance
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Primary variable: · Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids per patient per year
Key-secondary variable: · Mean change from baseline (V2) during the treatment period in post-bronchodilator FEV1
Secondary variables: COPD exacerbations · Mean rate of all COPD exacerbations per patient per year · Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids per patient per year (excluding hospitalizations) · Mean rate of COPD exacerbations requiring hospitalization per patient per year · Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids per patient per year in the population of patients with post-bronchodilator FEV1<30% of predicted at V2 · Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids per patient per year within the patient population with a mean cough score of ³ 2 and a mean sputum score of = 2 in the week directly preceding randomization · Proportion of patients experiencing a COPD exacerbation · Time to first COPD exacerbation treated with oral or parenteral steroids · Time to first COPD exacerbation requiring hospitalization · Time to second COPD exacerbation treated with oral or parenteral steroids · Mean number of COPD exacerbation days · Mean number of hospitalization days
Secondary variables: Spirometry parameters and others · Mean change from baseline (V2) after the treatment period in post-bronchodilator FEV1 · Mean change from baseline (V2) during and after the treatment period in pre-bronchodilator FEV1 · Mean change from baseline (V2) during and after the treatment period in spirometry parameters · Symptoms and use of rescue medication · Proportion of symptoms free days / rescue medication free days · Health care resource use · Transition Dyspnea Index Focal Scores (BDI/TDI) · EQ-5D
Safety: · Adverse events · Changes in laboratory values · Changes in physical examination findings including body weight and electrocardiograms (ECG) · Changes in vital signs blood pressure (BP) and heart rate (HR) · 24 hour holter monitoring (at selected centers in the US, in a subset of patients) · Hemoccult (guaiac) testing
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |